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Abstract:

A mixing system and mixing method are provided. The mixing system
includes a tank assembly, a container positioned within the tank
assembly, a mixer disposed within a compartment of the container, a
linear motor, and a shaft having a first end secured to the mixer and an
opposing second end secured to the linear motor. The linear motor
provides a variable stroke length for the shaft. The mixing method
includes providing a tank assembly having a linear motor, positioning a
mixing assembly including a mixing bag in the tank assembly, combining
two or more components in a compartment of the mixing bag, attaching a
mixing shaft extending from a mixer disposed within the mixing bag to the
linear motor, and raising and lowering the mixing shaft to mix the two or
more components. A stroke length of the mixing shaft during the raising
and lowering is varied.

Claims:

1. A mixing method, comprising: positioning a mixing assembly in a tank
assembly, the mixing assembly including a mixing bag, a mixer disposed
within the mixing bag, and a mixing shaft attached to the mixer and
extending from the mixing bag; dispensing two or more components in a
compartment of the mixing bag; and mixing the two or more components by
repeatedly raising and lowering the mixing shaft a stroke length, wherein
the stroke length of the mixing shaft is changed during the step of
mixing.

2. The method of claim 1, further comprising measuring a quality of at
least one of the two or more components in the compartment of the mixing
bag and changing the stroke length of the mixing shaft based on changes
in the measured quality.

3. The method of claim 2, further comprising using a measurement device
to measure the quality of the at least one of the two or more components,
the measurement device being in electrical communication with an
actuation mechanism that controls movement of the mixing shaft.

4. The method of claim 2, wherein the measured quality comprises a
thickness of a settlement of the at least one of the two or more
components within the mixing bag.

5. The method of claim 2, further comprising setting an initial stroke
length based on the measured quality.

6. The method of claim 2, wherein the quality is measured by an optical
sensor.

7. The method of claim 1, further comprising measuring a thickness of a
settlement of the at least one of the two or more components within the
mixing bag at different times.

8. The method of claim 7, further comprising varying the stroke length in
response to changes in the measured thickness of the settlement of the at
least one of the two or more components.

9. The method of claim 7, further comprising setting an initial stroke
length based on the measured thickness of the settlement of the at least
one of the two or more components.

10. The method of claim 9, further comprising increasing the stroke
length as the thickness of the measured settlement decreases.

11. The method of claim 1, further comprising changing the stroke length
during mixing according to a predetermined schedule.

12. The method of claim 1, further comprising adjusting the speed at
which the mixing shaft raises and lowers.

13. The method of claim 1, further comprising attaching the mixing shaft
to a linear motor and using the liner motor to raise and lower the mixing
shaft.

Description:

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a divisional of U.S. application Ser. No.
14/338,573, filed Jul. 23, 2014, which claims the benefit of and priority
to U.S. Provisional Patent Application No. 61/953,987 filed Mar. 17,
2014, which are hereby incorporated by reference in their entirety.

FIELD OF THE INVENTION

[0002] The present invention is directed to a mixing assembly and mixing
method. More specifically, the present invention is directed to a mixing
assembly having a variable stroke distance, and a mixing method including
a variable stroke distance.

BACKGROUND OF THE INVENTION

[0003] Culture media, buffers, reagents and other biological materials
(hereinafter "base materials") are used extensively by biotech companies
in research and development, creating vaccines, producing and purifying
proteins, and developing other biologicals. Many base materials include
precise compositions and are often highly regulated. Additionally, to be
safe and effective for their intended use, these base materials must be
pure and sterile. As such, the manufacture of base materials is expensive
and often requires specialized equipment.

[0004] Due to the huge expense of creating, operating, and maintaining the
elaborate systems used in the manufacture of base materials, biotech
companies frequently purchase the base materials in their final solution
form. However, in the solution form, the base materials often consist
primarily of water, and as such, can be difficult and expensive to
transport. Additionally, the final liquid solutions frequently have a
significantly shorter shelf life as compared to powdered base materials,
and must typically be stored under refrigerated conditions, which
increases the storage cost.

[0005] To decrease costs, the base materials may be shipped and/or stored
in their powdered form and mixed later. During the initial mixing with
the liquid, the powdered base materials are usually concentrated or
settled at the bottom of the mixing container. When concentrated or
settled at the bottom the powdered base materials may be difficult to
break up, and can damage the mixing device. One method of breaking up the
concentrated powdered base materials includes shaking the entire mixing
container. However, shaking the mixing container creates a risk for
disposable tank liners, and also presents limitations on the size of the
mixing container.

[0006] A mixing assembly and mixing method that show one or more
improvements in comparison to the prior art would be desirable in the
art.

BRIEF DESCRIPTION OF THE INVENTION

[0007] In an embodiment, a mixing system includes a tank assembly, a
container positioned within the tank assembly, a mixer disposed within a
compartment of the container, a linear motor, and a shaft having a first
end secured to the mixer and an opposing second end secured to the linear
motor. The linear motor provides a variable stroke length for the shaft.

[0008] In another embodiment, a mixing system includes a tank assembly
including a side wall and a floor defining a chamber, a container
positioned within the chamber, a mixer disposed within a compartment of
the container, a servo motor, a shaft having a first end secured to the
mixer and an opposing second end extending from the container and secured
to the servo motor, and a sensor to measure a thickness of a settlement
within the container. A stroke length of the servo motor is configured to
vary in length in response to measurements from the sensor.

[0009] In another embodiment, a mixing method includes providing a tank
assembly having a linear motor; positioning a mixing assembly in the tank
assembly, the mixing assembly including a mixing bag, a mixer disposed
within the mixing bag, and a mixing shaft attached to the mixer and
extending from the mixing bag; combining two or more components in a
compartment of the mixing bag; attaching the mixing shaft to the linear
motor; and raising and lowering the mixing shaft to mix the two or more
components. A stroke length of the mixing shaft during the raising and
lowering is varied.

[0010] An advantage of the mixing assembly, according to the embodiments
disclosed herein, includes decreasing stress on the mixing assembly when
settlements are present on the bottom of a mixing tank.

[0011] Another advantage includes increasing efficiency of the mixing
assembly.

[0012] Further advantages include increasing a lifespan of the mixing
assembly, decreasing risk to disposable tank liners, decreasing
limitations on the size of the mixing container, and combinations
thereof.

[0013] Other features and advantages of the present invention will be
apparent from the following more detailed description, taken in
conjunction with the accompanying drawings which illustrate, by way of
example, the principles of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0014] FIG. 1 is a perspective view of a mixing system.

[0015] FIG. 2 is a top view of a tank assembly.

[0016] FIG. 3A is a cross-sectional view of an adjustable floor in a
lowered position within a tank assembly according to an embodiment of the
disclosure.

[0017] FIG. 3B is a cross-sectional view of an adjustable floor in a
raised position within a tank assembly according to an embodiment of the
disclosure.

[0018] FIG. 4 is an exploded perspective view of a mixing bag assembly.

[0019] FIG. 5 is a bottom perspective view of a mixer according to an
embodiment of the disclosure.

[0020] FIG. 6 is a bottom perspective view of the mixer shown in FIG. 10
with the flaps thereof being downwardly flexed.

[0021] FIG. 7 is a cross-sectional view of a bottom end of a mixing bag
having a mixer disposed therein.

[0022] FIG. 8 is a partial cross-sectional view of a mixing assembly
having a solution disposed therein.

[0023] FIG. 9 is a top view of a mixing bag.

[0024] FIG. 10 is a cross-sectional view of a top end of a mixing bag.

[0025] FIG. 11 is a cross-sectional view of a top end of a mixing bag
including a cover plate according to an embodiment of the disclosure.

[0026] FIG. 12 is a side view of a feed bag coupled with a top end of a
mixing bag.

[0027] FIG. 13 is a side view of a spray nozzle.

[0028] FIG. 14 is a cross-sectional view of a spray nozzle disposed within
a port of a mixing bag.

[0029] Wherever possible, the same reference numbers will be used
throughout the drawings to represent the same parts.

DETAILED DESCRIPTION OF THE INVENTION

[0030] Referring to FIG. 1, in one embodiment, a mixing system 10, such
as, but not limited to, an imPULSE Mixing System available from Advanced
Scientifics Incorporated in Millersburg, Pa., is provided for mixing two
or more components, at least one of the components being liquid, so as to
produce a homogenous solution. In addition to at least one of the
components being liquid, other components of the two or more components
include, but are not limited to, liquids, gels, dry materials, or
combinations thereof. For example, in one embodiment, each of the two or
more components is liquid. In an alternate embodiment, one of the two or
more components is a liquid, such as water, and another component is a
dry or substantially dry material, such as powder, grain, granule, or
other form of solid.

[0031] The mixing system 10 is used to produce any suitable form of
solution, such as, but not limited to a sterile solution or a non-sterile
solution. Suitable solutions include, for example, culture media,
buffers, reagents, and other biological materials that may or may not be
sterile. In one embodiment, the two or more components are combined in
the mixing system 10 and mixed to form the solution. In another
embodiment, the mixing system 10 is used to produce a homogenous or
substantially homogenous solution from a solution that has settled, such
as, for example, a stored solution. In a further embodiment, the mixing
system 10 is adjustable based upon a settling of the solution.

[0032] In one embodiment, the mixing system 10 includes at least one
disposable component, such as a structural component that directly
contacts the solution during manufacture. In another embodiment, any of
the structural components contaminated by contact with the solution are
replaced with new components prior to the manufacture of different
batches and/or types of solutions. Based upon the type of solution, the
new components are either sterile or non-sterile. The use of the
disposable components reduces manufacturing time, down time, and/or
expense by reducing or eliminating sterilization or cleaning of the
mixing system 10. Alternatively, some or all of the components are
designed for sterilization and reuse.

[0033] In one embodiment, the mixing system 10 includes at least one tank
assembly 20 mounted on a platform 12, a mixing assembly 200 at least
partially disposed within the tank assembly 20, an actuation mechanism
170 detachably secured to the mixing assembly 200, and a filtration
system 500 in fluid communication with the mixing assembly 200. In
another embodiment, the platform 12 is a movable platform, on which some
or all of the components of the mixing system 10 are mounted. In a
further embodiment, the mixing system 10 is formed as a modular unit to
provide portability and ease of assembly. Alternatively, the mixing
assembly 200 is permanently assembled on site without the platform 12.

[0034] The at least one tank assembly 20 includes any suitable number of
tank assemblies having the same or different sizes, shapes, and/or
properties, each of the at least one tank assemblies 20 being mounted on
or off of the platform 12. In one embodiment, the tank assembly 20
includes a plurality of legs 22 upstanding from the platform 12 and
supporting an annular side wall 24. As illustrated in FIGS. 1 and 2, in
one embodiment, the side wall 24 has an interior surface 26 and an
exterior surface 28 each extending between an upper end 30 and an
opposing lower end 32. The interior surface 26 at least partially bounds
a chamber 60. The side wall 24 has a tubular configuration so that the
upper end 30 and the lower end 32 are open.

[0035] In another embodiment, the side wall 24 includes a body portion 23
having a substantially C-shaped transverse cross section. Other
transverse cross section shapes include, but are not limited to,
circular, polygonal, or hexagonal. In another embodiment, the polygonal
transverse cross section shape increases turbulent flow to provide
increased mixing of the two or more components. The body portion 23
terminates at substantially opposing end plates 54 and 56 with a doorway
57 formed therebetween. In one embodiment, to increase a hoop strength of
the body portion 23, a support brace 58 rigidly extends between the end
plates 54 and 56 at the lower end 32. In a further embodiment, the body
portion 23 includes an outer wall 34, a concentrically disposed inner
wall 36 and a central wall 38 concentrically disposed between the outer
wall 34 and the inner wall 36. The outer wall 34, the inner wall 36 and
the central wall 38 each connect with the end plates 54 and 56, as well
as extend between and rigidly connect with a top plate 70 and an opposing
bottom plate 72.

[0036] Disposed between the outer wall 34 and the central wall 38 is an
insulation layer 40. In one embodiment, the insulation layer 40 includes
an insulating material, such as, but not limited to, a chloride free,
ceramic fiber capable of withstanding temperatures of up to at least
1,300° C. In another embodiment, a door 25 is disposed within a
doorway 57 between the end plates 54 and 56. In a further embodiment, the
door 25 includes the outer wall 34, the inner wall 36, and the layer of
insulation 40 disposed therebetween. Hinges 50 secure the door 25 to the
body portion 23 to permit opening of the door 25, thus providing access
to the chamber 60. In one embodiment, a viewing window 48 disposed in a
viewing slot 46 on the door 25 provides an unobstructed view of the
chamber 60 when the door 25 is closed. The door 25 is locked in a closed
position by any suitable locking means, such as, but not limited to,
locking flanges 106 and stops, dead bolts, other interlocking members, or
a combination thereof.

[0037] Extending between the central wall 38 and the inner wall 36 of the
body portion 23 and/or the door 25 are a plurality of spaced apart
spacers 42. The spacers 42 include, for example, discrete members or
formations projecting from the central wall 38 and/or the inner wall 36.
The spacers 42 provide structural stability for both the central wall 38
and the inner wall 36, while permitting fluid to flow between the central
wall 38 and the inner wall 36, and around the spacers 42. The fluid
flowing between the central wall 38 and the inner wall 36 may be heated
or cooled to heat or cool a solution held within the chamber 60 of the
tank assembly 20. Additionally, the mixing system 10 may include a
temperature probe for continuously measuring the temperature of the
solution within the mixing bag 202. For example, in one embodiment, the
temperature probe continuously measures the surface temperature of the
mixing bag 202 to determine the temperature of the solution therein.

[0038] A floor 112 of the tank assembly 20 provides support for the mixing
assembly 200 when positioned thereon. A plurality of open port holes 116
and/or a central port hole 117 extend through the floor 112. In one
embodiment, a plurality of screened spill holes 118 is formed on the
floor 112. The floor 112 is circular, polygonal, elliptical, irregular,
flat, substantially flat, frustoconical, curved, pyramidal, conical, any
other configuration for supporting a bag, or a combination thereof. For
example, in one embodiment, the floor 112 includes a flat or
substantially flat portion 114, which is circular, and a peripheral wall
120 that slopes upwardly and outwardly from the flat or substantially
flat portion 114 to a terminal edge 122. Outwardly projecting from the
terminal edge 122 is a lip 124 that is either biased directly against or
terminates directly adjacent to the interior surface 26 of the side wall
24. In another embodiment, the floor 112 and the side wall 24 are made of
a metal, such as, for example, stainless steel. In a further embodiment,
the lip 124 is polypropylene, rubber, silicone, moldable plastic, any
other resilient material, or a combination thereof.

[0039] In one embodiment, as illustrated in FIGS. 2-3B, the floor 112 is
an adjustable floor having a strut 136 extending between the peripheral
wall 120 and a collar 134. A level of the adjustable floor is raised or
lowered relative to the side wall 24. In another embodiment, the
adjustable floor is raised or lowered, for example, by simultaneous
rotating one or more threaded members 130 positioned outside of the side
wall 24. The rotating of the one or more threaded members 130 raises or
lowers one or more of the collars 134 engaged therewith to raise or lower
the floor 112. Alternate embodiments include, but are not limited to,
raising or lowering the adjustable floor with chain drives, belt drives,
gear drives, hydraulic lifts, pneumatic lifts, jacks, cranks, winches,
pulley systems, any other suitable mechanism for raising or lowering
struts 136 extending from the exterior surface 28 of side wall 24, or a
combination thereof. The raising or lowering of the adjustable floor
relative to the side wall 24 adjusts a size of the chamber 60 bound by
the side wall 24 and the floor 112. For example, raising the adjustable
floor decreases the size of the chamber 60, while lowering the adjustable
floor increases the size of the chamber 60. In an alternate embodiment,
the floor 112 is fixed and does not raise or lower, thus fixing the size
of the chamber 60. The size of the chamber 60 includes, but is not
limited to, 5 liters, 20 liters, 250 liters, 500 liters, 750 liters,
1,000 liters, 1,500 liters, 3,000 liters, 5,000 liters, 10,000 liters, or
any other suitable size.

[0040] Referring to FIG. 4, in one embodiment, the mixing assembly 200
includes a mixing bag 202, such as, but not limited to, those sold by
Advanced Scientifics Incorporated of Millersburg, Pa., for use in
combination with its imPULSE Mixing System. In another embodiment, the
mixing assembly 200 includes a mixer 204, an expandable tubular seal 206,
and/or a mixing shaft 208. The mixing bag 202 provides a compartment 220
for containing the solution therein prior to, during, and/or after the
mixing of the two or more components. For example, in one embodiment, the
mixing bag 202 includes an elongated body 203 having an exterior surface
212 and an interior surface 210 that bounds the compartment 220. In
another embodiment, the mixing bag 202 includes any suitable combination
of plies, materials, thicknesses, panels 228, and/or seams 230 for
containing the solution therein, as described in U.S. Pat. No. 6,923,567,
which issued on Aug. 2, 2005, and is hereby incorporated by specific
reference. For example, the body 203 of one mixing bag includes a
flexible, water impermeable, single ply material having a thickness of
between about 0.1 mm to about 5 mm, and being formed from three or more
of the panels 228.

[0041] The body 203 and/or the compartment 220 of the mixing bag 202
include any shape, size, and/or configuration for being positioned within
the chamber 60 of the mixing system 10. For example, in one embodiment,
the body 203 includes a side wall 213 that, when the body 203 is inflated
or filled, has a substantially circular or rounded polygonal transverse
cross section extending between an upper end 214 and an opposing lower
end 216. The upper end 214 terminates at a top end wall 215 while the
opposing lower end 216 terminates at a bottom end wall 217. In another
embodiment, the body 203 bounds the compartment 220 sized to hold fluid
amounts, such as, but not limited to, 5 liters, 20 liters, 250 liters,
500 liters, 750 liters, 1,000 liters, 1,500 liters, 3,000 liters, 5,000
liters, 10,000 liters, or any other suitable amount.

[0042] Referring to FIGS. 5-6, the mixer 204 includes any article for
providing agitation and/or swirling of the solution within the mixing bag
202. For example, in one embodiment, the mixer 204 includes a base 205
having a threaded recess 252 for receiving the mixing shaft 208 therein.
In another embodiment, the base 205 includes flaps 264 movably mounted
thereon. The flaps 264 pivoting, for example, to provide mixing when
moved in one direction and fluid flow through the base 205 when moved in
an opposite direction. Other embodiments of the mixer 204 include, but
are not limited to, those disclosed in U.S. Pat. No. 6,923,567.

[0043] Referring to FIG. 7, the mixing shaft 208 includes a first end for
being secured to a threaded recess 252 of the mixer 204 within the mixing
bag 202, and an opposing second end for extending through the body 203 of
the mixing bag 202. For example, the second end of the mixing shaft 208
extends through the top end wall 215, the bottom end wall 217, or any
other portion of the body 203. In one embodiment, the mixing shaft 208 is
integral with the mixer 204 and forms a portion of the mixing assembly
200. Alternatively, the mixing shaft 208 is detachably secured to the
mixer 204 to form a separate component from the mixing assembly 200. In
one embodiment, more than one of the mixers 204 is secured to the mixing
shaft 208.

[0044] In one embodiment, the mixing shaft 208 extends through the
expandable tubular seal 206, which is positioned over a mounting port 242
on the top end wall 215 or the bottom end wall 217. The tubular seal 206
includes, but is not limited to, a first end 284, an opposing second end
286, and an expandable bellow section 288 extending therebetween. When
the mixing shaft 208 moves relative to the mixing bag 202, the bellow
section 288 selectively expands and contracts to maintain a seal
communication between the mixer 204 and the mounting port 242. By
maintaining the seal communication between the mixer 204 and the mounting
port 242, the expandable tubular seal 206 provides a fluid sealed
connection between the mixing bag 202 and the mixer 204 to prevent
leaking of the solution from the compartment 220 during mixing. Other
arrangements are also possible to prevent leaking of the solution from
the compartment 220.

[0045] Referring to FIGS. 1 and 8, an actuation mechanism 170 is provided
to move the mixer 204 attached to the mixing shaft 208 in a reciprocating
fashion (i.e., axial). The actuation mechanism 170 is detachably secured
to the second end of the mixing shaft 208 either directly or through one
or more connecting portions. For example, in one embodiment, the
actuation mechanism 170 operates an actuation rod 172, which is
detachably secured to the mixing shaft 208 through a coupler 176. The
actuation mechanism 170 is positioned in any suitable position relative
to the tank assembly 20 and/or the mixing assembly 200, based upon an
orientation of the mixing assembly 200 in the chamber 60. Suitable
positions of the actuation mechanism 170 include, for example, mounted on
or adjacent to the upper end 30 or the lower end 32, or along the side
wall 24 of the tank assembly 20. In one embodiment, when the mixing shaft
208 extends through the bottom end wall 217 and/or the central port hole
117 of the floor 112, the actuation mechanism 170 is mounted to a frame
168 that is secured to and extends below the floor 112. When mounted to
the frame 168, the actuation mechanism raises and lowers with the floor
112. In an alternate embodiment, the actuation mechanism 170 is mounted
on the platform 12 or a ground surface, such as, for example, when the
floor 112 is fixed in the tank assembly 20. In one embodiment, when the
mixing shaft 208 extends through the top end wall 215 the actuation
mechanism 170 is mounted and/or positioned adjacent to the upper end 30.
For example, in another embodiment, the actuation mechanism 170 is
mounted on a lift 400. To provide horizontal reciprocation of the mixing
shaft 208, the actuation mechanism 170 is positioned in any suitable
location along the side wall 24.

[0046] The actuation mechanism 170 includes any mechanism for varying a
stroke length of the mixing shaft 208. For example, in one embodiment,
the actuation mechanism 170 includes a linear motor, such as, but not
limited to, a servo motor, a linear actuator, air cylinders, any other
motor capable of a rapid change in direction, or a combination thereof.
Preferably, a servo motor is employed that can provide an infinitely and
continuously variable stroke length. In another embodiment, the actuation
mechanism 170 varies the stroke length of the mixing shaft 208 during
mixing of the solution within the mixing bag 202. For example, variation
of the stroke length includes, but is not limited to, continuous,
stepwise, pre-determined, measured, or a combination thereof.

[0047] In one embodiment, a method 300 of mixing the solution includes
positioning the mixing assembly 200 in the tank assembly 20 (step 301),
combining the two or more components in the compartment 220 of the mixing
bag 202 (step 303), and mixing the two or more components with the
actuation mechanism 170 to form the solution (step 305). The positioning
of the mixing assembly 200 in the tank assembly 20 (step 301) includes
inserting the mixing bag 202 within the chamber 60. In one embodiment,
prior to inserting the mixing bag 202 within the chamber 60, the floor
112 is raised or lowered to adjust the size of the chamber 60 based upon
an amount of solution to be manufactured. In another embodiment,
inserting the mixing bag 202 within the chamber 60 includes, for example,
connecting the lift 400 to a harness 296 (FIG. 9) secured to the body 203
of the mixing assembly 200, raising the mixing assembly 200 with the lift
400, guiding the mixing assembly 200 through the doorway 57, and lowering
the bottom end wall 217 of the mixing assembly 200 onto the floor 112
within the chamber 60. In an alternate embodiment, the mixing bag 202 is
manually inserted into the chamber 60 of the tank assembly 20.

[0048] During the lowering of the bottom end wall 217 onto the floor 112,
the features extending from the bottom end wall 217 are aligned with the
port holes 116 in the floor 112. When the mixing shaft 208 extends from
the bottom end wall 217, the mixing shaft 208 is aligned with and passed
through the central port hole 117 in the floor 112 during the lowering of
the bottom end wall 217 onto the floor 112. After inserting the mixing
bag 202 with the chamber 60 the mixing shaft 208 is coupled to the
actuation mechanism 170. When the mixing shaft 208 extends from the top
end wall 215, the mixing shaft 208 is coupled to the actuation mechanism
170 at any time after the mixing assembly 200 is detachably secured to
the lift 400.

[0049] Next, one or more tubes are coupled to features extending from the
bottom end wall 217 and/or the top end wall 215 of the mixing assembly
200. Referring to FIGS. 7 and 10-11, in one embodiment, the features
extending through the top end wall 215 and/or the bottom end wall 217 of
the mixing bag 202 provide fluid communication between the compartment
220 and the exterior. For example, referring to FIG. 7, in another
embodiment, an inflation portion 236, an outlet port 238, an inlet port
240, and a mounting port 242 are mounted on the bottom end wall 217, each
having a channel 227 extending therethrough to provide the fluid
communication. Referring to FIGS. 10-11, in a further embodiment, the
mixing bag 202 includes a feeding port 222, a fluid port 224, and a
pressure port 226 mounted on the top end wall 215 of the body 203, each
having the channel 227 extending therethrough. The channel 227 of each
port mounted on either the top end wall 215 or the bottom end wall 217 is
closed by any suitable sealing member, such as, but not limited to, an
extension sleeve 239, a removable clamp 245, a tie 241, a cover plate
232, or a combination thereof.

[0050] The plurality of features, alone or in combination, facilitate
filling, draining, and/or mixing of the solution within the compartment
220. In one embodiment, the feeding port 22, the fluid port 224, the
pressure port 226, the inflation port 236, the outlet port 238, and/or
the inlet port may facilitate filling and/or draining of the solution,
while the mounting port 242 receives the mixing shaft 208 therethrough to
facilitate mixing of the solution with the mixer 204. For example, in
another embodiment, a delivery tube 420 is coupled with the outlet port
238, the delivery tube 420 passing through or coupling with a first valve
422, a pump 424, a second valve 426, and a filtration system 500. In
another example, a sample tube 428 is coupled with the first valve 422,
and a return tube 430 extends between the second valve 426 and the inlet
port 240. In one embodiment, an air tube 432 is coupled with the
inflation port 236 and a gas source. The gas source provides compressed
gas, such as air, through the inlet port 240 to inflate the mixing bag
202. Once the mixing bag 202 is inflated, a fluid line 440 is coupled
with the fluid port 224. Alternatively, the fluid line 440 is coupled to
the fluid port 224 without coupling the air tube 432 to the inflation
port 236 and/or inflating the mixing bag 202.

[0051] During the inflating of the mixing bag 202, the providing the
components, and/or the dispensing of the solution, a pressure regulator
442 (FIG. 12) selectively controls a pressure within the mixing bag 202.
The pressure regulator 442 is coupled with the pressure port 226 and
includes an air inlet line 444 and an air outlet line 446. The air inlet
line is coupled to a pump or pressurized gas source to deliver air or
other gases into the mixing bag 202, and the air outlet line 446 to
permit gas to escape from the mixing bag 202 while maintaining a feed
component 603 within the mixing bag 202.

[0052] Referring to FIG. 12, subsequent to inserting the mixing bag 202,
the combining of the two or more components (step 303) includes providing
at least one of the two or more components to the compartment 220. For
example, in one embodiment, at least a portion of a fluid component 601,
such as water, is selectively dispensed into the compartment 220 through
the fluid line 440 coupled to the fluid port 224. In another embodiment,
the feed component 603, such as, but not limited to, the dry or
substantially dry material (e.g., culture media, buffers, or reagents in
a powder form) is dispensed into the compartment 220 from a feed bag 450
coupled to the feeding port 222. The fluid component and the feed
component 603 are dispensed separately and/or concurrently into the
compartment 220. Referring to FIGS. 13-14, in one embodiment, the fluid
component is dispensed through a spray nozzle 413 removably mounted to
the fluid port 224. The spray nozzle 413 provides a radial outward
spraying of the fluid component 601 to facilitate movement of feed
component particles that may have collected the side walls of the mixing
bag 202 and submersion of the feed component particles that may be
suspended or floating within the mixing bag 202.

[0053] During and/or subsequent to the providing at least one of the two
or more component to the compartment 220, the actuation mechanism 170 is
activated to move the mixer 204 in a reciprocating fashion. The raising
and lowering of the mixer 204 mixes the components to generate a
homogenous solution. In an alternate embodiment, the feed component 603
and/or the fluid component 601 are stored in the mixing bag 202 prior to
the positioning of the mixing assembly 200 or the activation of the
actuation mechanism 170. In another embodiment, during the storing of the
feed component 603 and/or the fluid component 601, one or more
particulates settle in the mixing bag 202 to form a settlement 605 at the
bottom of the compartment 220. The one or more particulates include, but
are not limited to, the feed component 603.

[0054] In one embodiment, the stroke length and/or speed provided by the
actuation mechanism 170 is varied to reduce or eliminate stress on the
mixer 204, the mixing shaft 208, and/or the actuation mechanism 170, from
the mixer 204 contacting the settlement 605. For example, in another
embodiment, the stroke length is reduced from a full stroke length 607 to
a reduced stroke length 609 by a distance equal to a thickness 608 of the
settlement 605. When the actuation mechanism 170 is mounted and/or
positioned adjacent to the upper end 30, reducing the stroke length
includes reducing the extension of the mixing shaft 208 towards the
bottom end wall 217. Alternatively, when the actuation mechanism 170 is
mounted and/or positioned adjacent to the lower end 32, reducing the
stroke length includes reducing the retraction of the mixing shaft 208
towards the bottom end wall 217. In a further embodiment, as the
settlement 605 breaks up the actuation mechanism 170 adjusts the stroke
length and/or speed until the settlement 605 is dissipated or the full
stroke length 607 and/or speed is reached. Additionally, the stroke
length and/or speed may be adjusted by the actuation mechanism 170 to
reduce or eliminate cell shear in the solution. For example, the stroke
length and/or speed may be adjusted to reduce or eliminate the formation
of air bubbles as the solution is mixed, which reduces or eliminates
damage to cells in the solution from the popping of the air bubbles.

[0055] The stroke length and/or speed is adjusted in any suitable manner,
such as, but not limited to, continuously (e.g., in response to changes
in measurements of the solution), incrementally, according to a
pre-programmed protocol and/or schedule, or a combination thereof. For
example, in one embodiment, the thickness 608 of the settlement 605 is
continuously measured, and the stroke length and/or speed are increased
in response to decreases in the thickness 608. The thickness 608 of the
settlement 605 is measured by any suitable measurement device 610, such
as, but not limited to, an optical interface sensor. The measurement
device 610 forms a portion of the tank assembly 10 and/or the mixing
assembly 200, is coupled to the actuation mechanism 170, and/or either
directly or indirectly provides measurements to the actuation mechanism
170.

[0056] In another embodiment, the actuation mechanism 170 adjusts the
stroke length and/or speed according to a pre-programmed schedule, such
as, but not limited to, a protocol based upon expected dissolution of the
settlement 605 and/or inclusion of additional components. The
pre-programmed protocol includes providing at least a first stroke length
and a first stroke speed for a first duration, and a second stroke length
and a second stroke speed for a second duration. Additional stroke
lengths and speeds may be provided for additional durations based up
solution characteristics such as, but not limited to, volume of the
solution, the components in the solution, an amount of the settlement, or
a combination thereof. Any suitable combination of stroke lengths, stroke
speeds, and/or durations is provided to mix the solution within the
mixing bag and or all of which may be varied or held constant with
respect to one another. For example, a protocol may include providing a
first stroke length of 3 inches for a duration of 5 minutes, followed by
a second stroke length of 5 inches for a duration of 10 minutes, while
the stroke speed remains constant.

[0057] The protocol may be determined based upon a variety of factors,
including the size of the tank assembly, the size of the mixing bag, the
volume of the solution in the mixing bag, the components in the solution,
the thickness of any settlement, solution viscosity, etc. For example,
solutions having thicker settlement may include decreased initial stroke
length, while solutions having decreased viscosity may have increased
stroke speed.

[0058] By varying the stroke length with the actuation mechanism 170, the
mixing system 10 provides a varied stroke length without adjusting the
center of a fixed crank. Additionally, the variable stroke length
decreases stress and/or damage to the mixing assembly 200 and/or the
actuation mechanism 170 after the settlement 605 has formed. Furthermore,
the variable stroke length decreases stress and/or damage to cells that
may be present in the solution.

[0059] Once the feed component 603 and the fluid component 601 are mixed
to form, for example, a homogenous or substantially homogenous solution,
the solution is either stored in the mixing bag 202 or dispensed from the
compartment 220. Dispensing the solution includes, but is not limited to,
dispensing through the delivery tube 420, passing through a filtration
system 500, passing through any other tube or system to exit the
compartment 220, or a combination thereof. In one embodiment, after
dispensing, the mixing bag 202 is refilled, disposed of, or recycled.
Refilling the mixing bag 202 may include sterilizing the mixing assembly
200 and/or replacement of one or more components of the mixing assembly
200.

[0060] While the invention has been described with reference to one or
more embodiment, it will be understood by those skilled in the art that
various changes may be made and equivalents may be substituted for
elements thereof without departing from the scope of the invention. In
addition, many modifications may be made to adapt a particular situation
or material to the teachings of the invention without departing from the
essential scope thereof. Therefore, it is intended that the invention not
be limited to the particular embodiment disclosed as the best mode
contemplated for carrying out this invention, but that the invention will
include all embodiments falling within the scope of the appended claims.

Patent applications by Rudolf Pavlik, Millersburg, PA US

Patent applications in class WITH TEST, SIGNAL, OR INDICATOR MEANS

Patent applications in all subclasses WITH TEST, SIGNAL, OR INDICATOR MEANS